Short-term administration of fluoxetine and venlafaxine decreases corticosteroid receptor mRNA expression in the rat hippocampus
Abstract
Chronic treatment with antidepressant drugs (2 weeks or longer) increases corticosteroid receptor mRNA expression in the hippocampus and reduces hypothalamic-pituitary-adrenal axis activity in parallel with improving mood and neuroendocrine function. Earlier effects are less well documented. We examined the effects of short term (9 days) treatment with fluoxetine (10 mg/kg) and venlafaxine (10 mg/kg) on hippocampal mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA expression and spatial memory in adult rats. In situ hybridization histochemistry showed that the antidepressants decreased MR mRNA expression in all hippocampal subregions (e.g. 45% decrease in CA1 with venlafaxine, P<0.001), while GR mRNA expression was selectively reduced in the CA3 subregion. There was a trend for decreased plasma corticosterone levels following fluoxetine (50% fall, P=0.07) and venlafaxine (30% fall, P=0.18) but neither antidepressants affected spatial memory in the watermaze. Thus antidepressants can have complex and opposing actions on hippocampal corticosteroid receptor expression depending on the duration of treatment.
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The decrease in GR expression by sertraline is in line with reports from literature in cell culture and animal studies.
“This is in line with reports from the literature in both cell culture and animal studies,23, 51, 61”
From Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor (2011) · cites this paper as [61]
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- Authors
- Yau, J. L. W., Noble, J., Hibberd, C., & Seckl, J. R.
- Affiliations
- Western General Hospital (GB)
- Corresponding author
- Yau, Joyce L.W
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2001-06
- Volume
- 306
- Issue
- 3
- Pages
- 161-164
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2027775989
- Cited by
- 43
- References
- 19
- Citations by year
- 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 3
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fluoxetine, venlafaxine, antidepressants, mineralocorticoid receptor, glucocorticoid receptor, hippocampus, spatial memory, corticosterone, hypothalamic-pituitary-adrenal axis, hippocampal subfields
- MeSH terms
- Venlafaxine Hydrochloride, Animals, Corticosterone, Cyclohexanols, Fluoxetine, Hippocampus, Male, Memory, Rats, Inbred Strains, Receptors, Glucocorticoid, RNA, Messenger, Gene Expression, Receptors, Mineralocorticoid, Antidepressive Agents, Second-Generation, Maze Learning, Rats
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